This invention relates to an anti-HIV (human immunodeficiency virus) peptide and a modified anti-HIV peptide.
The anti-HIV peptide of the present invention functions to inhibit infection of HIV (human immunodeficiency virus) and may be applied to treatment or prevention of manifestation of acquired human immunodeficiency syndromes (AIDS).
As a drug or medicament for treatment or prevention of manifestation of AIDS by HIV, inhibitors for reverse transcriptase owned intrinsically by HIV and necessitated for replication of the virus particles, are practically used. However, these inhibitors are not desirable because of the powerful toxicity thereof against the normal cells. Although proper vaccination may be thought of as a measure against the manifestation of the disease, difficulties are met in the evolution of a proper vaccine because the antigenicity of the protein covering the outer surface of the HIV may be changed easily by mutation and no reports have been made on the examples of success in the evolution of suitable vaccines.
Thus, the evolution of drugs or medicaments which are more powerful and lower in toxicity is progessing briskly. For example, various medicaments have been proposed for preventing the infection by inhibiting the binding of HIV to the cells.
A first one of such medicaments is an antibody capable of being bound to gp 120 or gp 41 which is the protein covering the outer surface of HIV. Such antibody may be prepared in the form of an antiserum or as a monoclonal antibody by inoculating a suitable animal with the protein. However, since the antigenicity of the above mentioned protein is not necessarily constant, it is necessary to find an antibody against the amino acid sequence which is not subject to variation. Moreover, since the usually available antibody is derived from animals, the antibody itself exhibits immunogenicity with respect to a human so that the antibody cannot be used repeatedly.
In the second place, it has been attempted to administer an antibody against the CD4 molecule, which is the HIV receptor on the cell, to thereby sheath the cell for exempting the cell from infection by HIV. Although the HIV may be prevented from being bound to the cell, the function of the normal cells is affected simultaneously.
In the third place, it has been attempted to apply the CD4 molecule itself, which is the HIV receptor, to the treatment for obviating the problem in employing the antibody. It is generally recognized that the CD4 molecule, which is soluble, is effective to prevent propagation of infection by binding the gp 120 of HIV, while not interfering with the function of normal cells, such as that of macrophages, or the class II specific interaction among the T cells. This soluble CD4 molecule has already been prepared by application of a genetic engineering technique (Hussey, R.E. et al., Nature, 331, 78, 1988).
However, the soluble CD4 molecule, when used actually as the anti-HIV drug, presents problems in connection with the shortness of the time period during which the efficacy of the drug in the blood is reduced to half, non-sustained efficacy and larger dosage. Thus, it has been felt necessary to improve the soluble CD4 molecule (Capon, D.J.et al., Nature, 337, 525-531, 1989).
In the fourth place, a method has been proposed which takes advantage of a region of the peptide of the CD4 molecule capable of being specifically bound with the gp 120 of HIV. This peptide is comprised only of a portion taking part in binding with gp 120 and may be bound with gp 120 in the same manner as is the soluble CD4 molecule so that the peptide is highly unlikely to be involved in any other unnecessary reactions and hence exhibits high specificity. Also, this peptide may be prepared easily as drugs in various ways, since it is prepared by chemical synthetic methods. As such chemically synthesized peptide, a peptide having 63 amino acid residues has been proposed, as in Hayashi, Y. et al., Archives of Virology, 105, 129-135, 1989. This peptide, however, is inconvenient since it cannot be mass-produced without difficulties by the peptide synthesis technique because of its longer amino acid chain length. Another peptide having 19 amino acid residues has also been proposed by Lisfson, J.D. et al., Science, 241, 712-716, 1988. Although shorter in amino acid chain length, this peptide is not satisfactory in anti-HIV activity. Thus, there is a strong demand for a peptide which has a shorter amino acid chain length and yet is superior in anti-HIV activity.